Article
Chemistry, Multidisciplinary
Alvaro M. Martins, Tania M. Lopes, Francisca Diniz, Jose Pires, Hugo Osorio, Filipe Pinto, Daniela Freitas, Celso A. Reis
Summary: Alterations in glycosylation machinery in cancer cells lead to the synthesis of abnormal glycan structures in tumor cells. Extracellular vesicles (EVs) are involved in cancer communication and progression, and certain tumor-associated glycans have been identified in cancer EVs. This study investigates the impact of 3D tumor architecture on the selective packaging of cellular glycans into EVs. The results show differential packaging of specific proteins and glycans in EVs produced by 2D and 3D cultured cells, suggesting distinct biological functions and correlation with clinical data.
Article
Biotechnology & Applied Microbiology
Shelly Martin, Russell McConnell, Rane Harrison, Su Chul Jang, Chang Ling Sia, Sushrut Kamerkar, Anna Duboff, Lisa Jacob, Jonathan Finn, Scott Estes
Summary: Extracellular vesicles (EVs) are a new therapeutic modality that can deliver various molecules to treat diseases. By conducting high-throughput siRNA screens, we have identified genetic pathways that regulate EV productivity and found that inhibiting cholesterol synthesis can significantly increase EV production. This strategy is also applicable to mesenchymal stem cells (MSCs).
BIOTECHNOLOGY AND BIOENGINEERING
(2023)
Review
Biochemistry & Molecular Biology
Ciarra Almeria, Sebastian Kress, Viktoria Weber, Dominik Egger, Cornelia Kasper
Summary: Extracellular vesicles (EVs) are cell-derived membrane structures that play a major role in physiological and pathological processes by delivering biomolecules to target cells. Many effects previously attributed to cell-based therapies are actually mediated by EVs, suggesting the use of purified EVs instead of living cells for therapy. This review focuses on the heterogeneity of EVs derived from mesenchymal stem/stromal cells (MSC) and summarizes the upstream parameters that critically affect their therapeutic properties and biological functions.
CELL AND BIOSCIENCE
(2022)
Article
Medicine, Research & Experimental
Britt Hanson, Ioulia Vorobieva, Wenyi Zheng, Mariana Conceicao, Yulia Lomonosova, Imre Mager, Pier Lorenzo Puri, Samir El Andaloussi, Matthew J. A. Wood, Thomas C. Roberts
Summary: Extracellular vesicles (EVs) play an important role in the regulation of myogenic differentiation. Inhibition of exosome biogenesis and EV uptake reduces myoblast differentiation, while treatment with conditioned medium enhances myogenic differentiation. Purified EVs promote myogenic differentiation at low doses but inhibit it at high doses. Muscle-enriched miRNAs are scarce in EVs, suggesting a myomiR-independent mechanism underlying the pro-myogenic effects of EVs.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2023)
Article
Chemistry, Multidisciplinary
Junli Zhang, Yifan Zhu, Mengting Guan, Yingying Liu, Min Lv, Chongwei Zhang, Hongling Zhang, Zhenzhong Zhang
Summary: Exosomes have potential as cancer biomarkers in clinical applications, but enrichment and detection from complex media remain challenging. This study used iodixanol density gradient centrifugation for exosome isolation and purification, and surface plasmon resonance (SPR) biochip for label-free detection of exosomal PD-L1. The method showed better specificity in distinguishing exosomes with different levels of PD-L1 compared to enzyme-linked immunosorbent assays.
Article
Multidisciplinary Sciences
Dimitra Panagaki, Jacob T. Croft, Katharina Keuenhof, Lisa Larsson Berglund, Stefanie Andersson, Verena Kohler, Sabrina Buttner, Markus J. Tamas, Thomas Nystrom, Richard Neutze, Johanna L. Hoog
Summary: Nuclear envelope budding (NEB) is an alternative pathway for nucleocytoplasmic communication that is evolutionarily conserved from early protists to human cells. In yeast cells, NEB events occur more frequently under stress conditions such as heat shock, exposure to harmful chemicals, and inhibition of the proteasome. NEB may play a role in aiding the transport of protein aggregates across the nuclear envelope, particularly in response to protein misfolding and heat shock.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Cristina Mas-Bargues, Consuelo Borras
Summary: The progress in understanding the biological properties of extracellular vesicles (EVs) derived from stem cells has been hindered by many misconceptions and methodological issues. Standardization of methodology is necessary in order to compare, validate, and improve the reliability and credibility of the various research findings for the development of EV-based therapeutics.
FREE RADICAL BIOLOGY AND MEDICINE
(2021)
Article
Cell Biology
Tom G. Keulers, Sten F. Libregts, Joel E. J. Beaumont, Kim G. Savelkouls, Johan Bussink, Hans Duimel, Ludwig Dubois, Marijke Zonneveld, Carmen Lopez-Iglesias, Karel Bezstarosti, Jeroen A. Demmers, Marc Vooijs, Marca Wauben, Kasper M. A. Rouschop
Summary: GABARAPL1 is essential for cargo loading and secretion of extracellular vesicles, with GABARAPL1(+)EVs being detectable and targetable for blocking pro-angiogenic effects. Silencing GABARAPL1 results in impaired early endosomal pathway and secretion of EVs with pro-angiogenic properties, affecting tumor growth and therapy efficacy.
JOURNAL OF EXTRACELLULAR VESICLES
(2021)
Article
Pharmacology & Pharmacy
Wei Heng Chng, Ram Pravin Kumar Muthuramalingam, Charles Kang Liang Lou, Silas New, Yub Raj Neupane, Choon Keong Lee, Ayca Altay Benetti, Chenyuan Huang, Praveen Thoniyot, Wei Seong Toh, Jiong-Wei Wang, Giorgia Pastorin
Summary: Extracellular vesicles (EVs) are miniaturised carriers that naturally secrete functional proteins, lipids, and nucleic acid material and have intrinsic pharmacological effects in human diseases. However, their low isolation yield and laborious purification process hinder their clinical translation. To overcome this, our lab developed cell-derived nanovesicles (CDNs), mimetics of EVs created by shearing cells through membrane-fitted spin cups. We compared the physical properties and biochemical composition of monocytic U937 EVs and U937 CDNs to evaluate their similarities. CDNs exhibited similar hydrodynamic diameters and shared proteomic, lipidomic, and miRNA profiles with natural EVs. Furthermore, CDNs exhibited similar pharmacological activities and immunogenicity to EVs when administered in vivo. CDNs could be a scalable and efficient alternative to EVs in clinical use.
Article
Immunology
Benjamin D. S. Clarkson, Ethan Grund, Kenneth David, Renee K. Johnson, Charles L. Howe
Summary: The causes of grey matter pathology and diffuse neuron injury in multiple sclerosis (MS) are not fully understood. This study found that axonal stress signals from white matter lesions may play a role in initiating diffuse grey matter pathology. The researchers analyzed the transcriptome of actively translating neuronal transcripts in mouse models of demyelinating disease and identified upregulated genes associated with the ISGylation pathway. They also noted changes in neuronal extracellular vesicle protein and miRNA cargo, with a skewed distribution towards proinflammatory and neurotoxic miRNAs.
JOURNAL OF NEUROINFLAMMATION
(2022)
Article
Cell Biology
Luisa Loconte, Davinia Arguedas, Rojbin El, Alix Zhou, Anna Chipont, Lea Guyonnet, Coralie Guerin, Ester Piovesana, Jose Luis Vazquez-Ibar, Alain Joliot, Clotilde Thery, Lorena Martin-Jaular
Summary: Cell-cell communication within the complex tumor microenvironment is critical to cancer progression. This study focuses on the role of tumor-derived extracellular vesicles (TD-EVs) in modulating immune cells and analyzes the impact of different labeling methods on the detection of EVs' interaction with immune cells. The results show that different labeling methods lead to diverging results and influence the detection of different types of EV interactions with recipient cells.
JOURNAL OF EXTRACELLULAR VESICLES
(2023)
Article
Biochemistry & Molecular Biology
Anne M. Skelton, D. Joshua Cohen, Barbara D. Boyan, Zvi Schwartz
Summary: This study aimed to investigate the characteristics of osteoblast-derived matrix vesicles (MV) in the regulation of extracellular vesicles and osteoblast differentiation, and to assess their mechanism of uptake. The results showed that MVs exhibited increased alkaline phosphatase activity, specific size and membrane protein markers, and played a regulatory role in osteoblast differentiation and production of inflammatory markers. The uptake of MVs by osteoblasts was found to involve a vesicular transport mechanism. These findings support the hypothesis that osteoblast-derived MVs participate in the regulation of osteogenesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Bianca Cruz Pachane, Ana Carolina Caetano Nunes, Thais Regiani Cataldi, Kelli Cristina Micocci, Bianca Caruso Moreira, Carlos Alberto Labate, Heloisa Sobreiro Selistre-de-Araujo, Wanessa Fernanda Altei
Summary: Hypoxia in triple-negative breast tumors promotes the secretion of extracellular vesicles, which enhance cell invasion. In this study, we investigated the invasive properties triggered by hypoxic small EVs derived from TNBC tumors. The results showed that hypoxic EVs have increased protein abundance and diversity, and are enriched in pro-invasive pathways.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Engineering, Biomedical
Lilibeth Ortega-Pineda, Alec Sunyecz, Ana I. Salazar-Puerta, Maria Angelica Rincon-Benavides, Diego Alzate-Correa, Amrita Lakshmi Anaparthi, Elizabeth Guilfoyle, Louisa Mezache, Heather L. Struckman, Silvia Duarte-Sanmiguel, Binbin Deng, David W. McComb, Daniel J. Dodd, William R. Lawrence, Jordan Moore, Jingjing Zhang, Eduardo Reategui, Rengasayee Veeraraghavan, M. Tyler Nelson, Daniel Gallego-Perez, Natalia Higuita-Castro
Summary: Gene/oligonucleotide therapies have shown potential as a treatment strategy for neurological conditions, but current delivery methods have limitations. Extracellular vesicles (EVs) have emerged as a promising delivery vehicle, overcoming many of these limitations, including low permeability of the blood-brain barrier. This study provides a detailed understanding of the manufacturing process of neurogenic EVs and demonstrates their ability to enhance neuron-specific tropism and modulate electrophysiological activity. The study also suggests that surface decoration with glutamate receptors can facilitate enhanced delivery of EVs to the brain. Overall, these findings suggest that designer EVs loaded with specific factors can be a promising nanotechnology platform to drive pro-neuronal responses.
ADVANCED HEALTHCARE MATERIALS
(2022)
Article
Cell Biology
Natalie J. Foot, Macarena B. Gonzalez, Kelly Gembus, Pamali Fonseka, Jarrod J. Sandow, Thuy Tien Nguyen, Diana Tran, Andrew I. Webb, Suresh Mathivanan, Rebecca L. Robker, Sharad Kumar
Summary: Studies have shown that Arrdc4 is involved in the normal development and maturation of sperm, affecting sperm function by controlling the biogenesis and release of extracellular vesicles.
JOURNAL OF EXTRACELLULAR VESICLES
(2021)
Editorial Material
Gastroenterology & Hepatology
Roberto Gramignoli
JOURNAL OF HEPATOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Rujie Sun, Xin Song, Kun Zhou, Yuyang Zuo, Richard Wang, Omar Rifaie-Graham, David J. Peeler, Ruoxiao Xie, Yixuan Leng, Hongya Geng, Giulia Brachi, Yun Ma, Yutong Liu, Lorna Barron, Molly M. Stevens
Summary: This study presents a versatile platform for fabricating fillable microrobots using microfluidic loading and dip sealing (MLDS), which allows for encapsulating different types of cargoes within hollow microrobots and protecting the cargo integrity. The technique is supported by high-resolution 3D printing and an integrated microfluidic loading system, enabling a highly precise loading process and improved cargo loading capacity. The MLDS platform offers new opportunities for targeted drug delivery, environmental sensing, and chemically powered micromotor applications.
ADVANCED MATERIALS
(2023)
Article
Chemistry, Multidisciplinary
Omar Rifaie-Graham, Jonathan Yeow, Adrian Najer, Richard Wang, Rujie Sun, Kun Zhou, Tristan N. Dell, Christopher Adrianus, Chalaisorn Thanapongpibul, Mohamed Chami, Stephen Mann, Javier Read de Alaniz, Molly M. Stevens
Summary: This study describes a non-equilibrium nanosystem that utilizes light-gated chemical communication, controllable feedback, and macroscopic oscillations. The system allows for communication between nanoreactors and induces chemical mechanical oscillations in a hydrogel using feedback loops.
Article
Hematology
Daniel W. Hagey, Egle Kvedaraite, Mira Akber, Andre Goergens, Joman Javadi, Tatiana von Bahr Greenwood, Caroline Bjorklund, Selma Olsson Akefeldt, Tova Hannegard-Hamrin, Henrik Arnell, Katalin Dobra, Nikolas Herold, Mattias Svensson, Samir El Andaloussi, Jan-Inge Henter, Magda Lourda
Summary: This study compared monocyte-derived dendritic cells from LCH patients to those from healthy controls or patients with Crohn's disease. The findings showed that LCH cells exhibited increased endo- and exocytosis gene activity and the enrichment of pathological transcripts in extracellular vesicles. The study also indicated that the LCH secretome had a significant effect on lymphocyte activity.
Article
Oncology
Erik Boberg, Nadir Kadri, Daniel W. W. Hagey, Lilly Schwieler, Samir El Andaloussi, Sophie Erhardt, Ellen Iacobaeus, Katarina Le Blanc
Summary: Murine studies indicate that after aHSCT, donor-derived macrophages replace damaged microglia and alloreactive T-cells invade the central nervous system. In this study, CNS immune surveillance and metabolic activity were assessed in relation to cognitive dysfunction and fatigue in aHSCT patients. The results showed increased proportions of activated T-cells and CD16+ NK-cells in the cerebrospinal fluid of patients with cognitive dysfunction. Immune cell activation was accompanied by reduced levels of anti-inflammatory factors and an upregulation of apoptosis pathway genes. The study suggests potential treatment targets for post-transplant CNS inflammation and neurotoxicity.
Article
Biotechnology & Applied Microbiology
Taras Sych, Jan Schlegel, Hanna M. G. Barriga, Miina Ojansivu, Leo Hanke, Florian Weber, R. Beklem Bostancioglu, Kariem Ezzat, Herbert Stangl, Birgit Plochberger, Jurga Laurencikiene, Samir El Andaloussi, Daniel Fuerth, Molly M. Stevens, Erdinc Sezgin
Summary: Lipid nanoparticles, viruses, exosomes and liposomes can be characterized using fluorescence fluctuations analysis. A method called single-particle profiler is introduced to provide information on the content and biophysical properties of thousands of particles within the size range of 5-200 nm. The single-particle profiler is utilized to measure mRNA encapsulation efficiency of lipid nanoparticles, viral binding efficiencies of different nanobodies, and the biophysical heterogeneity of liposomes, lipoproteins, exosomes and viruses.
NATURE BIOTECHNOLOGY
(2023)
Article
Multidisciplinary Sciences
Sebastien J. P. Callens, Daniel Fan, Ingmar A. J. van Hengel, Michelle Minneboo, Pedro J. Diaz-Payno, Molly M. Stevens, Lidy E. Fratila-Apachitei, Amir A. Zadpoor
Summary: The organization of bone cells in landscapes with varying curvatures was studied, revealing a preference for local concavities, multicellular bridging, and collective stress fiber orientation.
NATURE COMMUNICATIONS
(2023)
Article
Engineering, Biomedical
Hongya Geng, Emily J. Lupton, Yun Ma, Rujie Sun, Christopher L. Grigsby, Giulia Brachi, Xiaorui Li, Kun Zhou, Daniel J. Stuckey, Molly M. Stevens
Summary: The development of near-infrared light responsive conductive polymers provides a useful theranostic platform for malignant tumors. The self-assembly of ultrathin 2D polypyrrole nanosheets with tunable size distribution enables photoacoustic imaging and photothermal therapy. The pH-responsive features of the nanosheets show potential for accurate and highly efficient theranostics.
ADVANCED HEALTHCARE MATERIALS
(2023)
Article
Chemistry, Multidisciplinary
Wei Jun Chen, Dhanu Gupta, Meiyang Yang, Fuwei Yang, Ning Feng, Junling Song, Matthew J. A. Wood, Lipeng Qiu, Jinghua Chen
Summary: Metal-organic frameworks (MOFs) with tunable porosity, biocompatibility, and modularity have shown promise as novel therapeutics for malignancies. However, the design and synthesis of dual-stimuli responsive MOFs for controlled drug release in tumor microenvironments are challenging. This study synthesized pH/glutathione (GSH)-sensitive MnFe-based MOFs combined with gold nanoparticles (Au NPs) and cisplatin prodrugs (DSCP) for chemo-chemodynamic-starvation synergistic therapy.
Article
Multidisciplinary Sciences
Junfang Zhang, Yuntao Zhu, Christian Njel, Yuxin Liu, Pietro Dallabernardina, Molly M. Stevens, Peter H. Seeberger, Oleksandr Savateev, Felix F. Loeffler
Summary: In this study, a new synthesis strategy for carbon nitride photoelectrodes was introduced through advanced film generation techniques. This method involved spin coating pretreatment of a conductive substrate with a multipurpose polymer and a supramolecular precursor, followed by chemical vapor deposition to synthesize dual-layer carbon nitride photoelectrodes. The polymer improved the polymerization degree and electrical conductivity of carbon nitride, leading to state-of-the-art photoelectrochemical performance and high yields in C-H functionalization.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Wenyi Zheng, Julia Raedler, Helena Sork, Zheyu Niu, Samantha Roudi, Jeremy P. P. Bost, Andre Goergens, Ying Zhao, Doste R. R. Mamand, Xiuming Liang, Oscar P. B. Wiklander, Taavi Lehto, Dhanu Gupta, Joel Z. Z. Nordin, Samir EL Andaloussi
Summary: This study conducted a large-scale screening to identify potential scaffold proteins for loading therapeutic cargo into extracellular vesicles (EVs). They found 24 proteins with conserved EV-sorting abilities, including TSPAN2 and TSPAN3 which outperformed the well-studied CD63 scaffold. These engineered EVs showed promise as delivery vehicles in cell cultures and mice.
NATURE COMMUNICATIONS
(2023)
Article
Biochemical Research Methods
Vernon LaLone, Aleksandra Aizenshtadt, John Goertz, Froydis Sved Skottvoll, Marco Barbero Mota, Junji You, Xiaoyu Zhao, Henriette Engen Berg, Justyna Stokowiec, Minzhi Yu, Anna Schwendeman, Hanne Scholz, Steven Ray Wilson, Stefan Krauss, Molly M. Stevens
Summary: Confocal Raman spectral imaging (RSI) enables label-free visualization of molecules in biological specimens without sample preparation. qRamanomics, an integrated bioanalytical methodology, is developed to quantify the deconvoluted spectra for quantitative spatial chemotyping of biomolecules. It is applied to assess specimen variation and maturity in 3D liver organoids and identify biomolecular response signatures from liver-altering drugs, facilitating drug metabolism and accumulation monitoring.
CELL REPORTS METHODS
(2023)